Abstract
The demographics of Western populations are changing, with an increase in the proportion of older adults. There is evidence to suggest that genetic factors may influence the aging process: studying these may lead to interventions to help individuals live a longer and healthier life. Evidence from several groups indicates that Klotho (KL), a gene encoding a single-pass transmembrane protein that acts as an FGF23 co-receptor, may be associated with longevity and healthy aging. We aimed to explore this area further by comparing the genotype counts in 642 long-lived individuals from the Newcastle 85+ Study with 18 295 middle-aged Newcastle-based controls from the UK Biobank to test whether variants at the KL gene locus are over- or under-represented in older individuals. If KL is associated with longevity, then we would expect the genotype counts to differ between the 2 cohorts. We found that the rs2283368 CC genotype and the rs9536338 C allele, but not the KL-VS haplotype, were associated with reaching very old age. However, these associations did not replicate in the remainder of the UK Biobank cohort. Thus, our results do not reliably support the role of KL as a longevity factor.
Highlights
The demographics of Western populations are changing, with an increase in the proportion of older adults
Since the 2 variants making up the KL-VS haplotype are wellcharacterized functional KL variants in humans, we investigated whether or not their genotype distributions differed significantly between N85+ participants and Newcastle UK Biobank (UKB) participants (Table 1)
It has been suggested that KL-VS heterozygotes are at an advantage when it comes to longevity
Summary
The demographics of Western populations are changing, with an increase in the proportion of older adults. KL is located on chromosome 13 in humans and encodes a single-pass transmembrane protein that acts as an FGF23 co-receptor [2,3,4] It was first identified in mice by Kuro-o et al [5], who showed that decreased kl expression resulted in a condition resembling premature aging. Since this discovery, multiple studies have been carried out to explore the relationship between genetic variants at the KL gene locus and longevity. Novelli et al [9] compared U.S participants aged between 99 and 111 years old to controls aged
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